Risk of post-radiation hypothyroidism among different head and neck cancer subsites and radiation therapy techniques

Hypothyroidism is a common complication in head and neck cancer (HNC) patients after radiotherapy (RT). This study aimed to investigate the risk of hypothyroidism after RT in HNC patients and compare risks among different HNC subsites and RT techniques. This retrospective cohort study included 1038 HNC patients treated with RT, categorized into nasopharyngeal carcinoma (NPC) and non-NPC groups, then further divided by RT type into volume modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT). Hypothyroidism was defined as increased thyroid-stimulating hormone with decreased free T4 or initiation of thyroxine therapy. Kaplan-Meier and Cox regression analyses were performed to compare the risk of hypothyroidism across HNC subsites and RT techniques. The NPC and non-NPC groups had similar post-RT hypothyroidism risks (p = 0.340). In non-NPC HNCs, hypopharynx/larynx cancer patients had the highest incidence rate (73.7 per 1000 patient-year) and risk compared to others. Among NPC patients, the risk of hypothyroidism did not differ significantly between IMPT and VMAT (adjusted hazard ratio AHR: 1.56, 95% confidence interval CI: 0.98-2.48). However, among non-NPC patients, those treated with IMPT had higher risk of hypothyroidism than VMAT (AHR: 1.96, 95% CI: 1.18-3.24), particularly in the hypopharynx/larynx subgroup (AHR: 3.77, 95% CI: 1.67-8.47). Patients with hypopharyngeal or laryngeal cancer might have an increased risk of hypothyroidism after radiotherapy, with a more pronounced association observed among those treated with IMPT. These findings should be interpreted cautiously given the limited subgroup size. Nevertheless, heightened clinical awareness of hypothyroidism might be warranted in these patients.